Costo-efficacia di rituximab nella terapia di mantenimento in soggetti affetti da linfoma non-Hodgkin follicolare refrattario o recidivante
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Cost-effectiveness of rituximab in maintenance treatment of refractory or relapsing follicular non-Hodgkin lymphoma
Objectives: Scope of this analysis was to estimate the cost-effectiveness of rituximab maintenance (r-maintenance) therapy vs. observation, in relapsed/refractory follicular lymphoma patients following response to induction therapy with or without rituximab, based on data from a large multicenter study, in the Italian public payer’s perspective.
Methods: This study models the impact of r-maintenance vs. observation using a 15 years, health-state transition model. All patients entered the model following response to chemotherapy with or without rituximab as induction therapy (progression-free health state, PFHS). On the basis of probability estimates derived from the clinical trial, the model simulates transitions of patients from PFHS to either progressed health state (PHS) or death. Progression-free survival (PFS) and overall survival (OS) following r-maintenance are extrapolated from 2-year Kaplan-Meier curves from the study data (median trial follow-up 31 months) using a Weibull distribution (in the basecase PFS and OS clinical benefit is assumed to last 5 years). Quality of life utility values for the health states in the model were derived from a study of 165 patients using the EQ-5D questionnaire. Direct medical costs (including drug acquisition plus administration and management of adverse events) are reported in 2006 Euros and are derived from expert opinion and published sources. Costs and outcomes were discounted at a rate of 3.5%. In order to address uncertainty in point estimates, one-way and probabilistic sensitivity analyses were also performed.
Results: The estimated lifetime incremental PFS is a 1.5 year increase for r-maintenance vs. observation (3.2 vs. 1.7 years). Overall survival analysis (based on 5 year extrapolation of the clinical benefit) yields an estimate of 5.9 life years (LY) for r-maintenance vs. 4.9 for observation (difference 0.99 LY gained). Total cost for r-maintenance is estimated as €26,027 vs. €16,146. R-maintenance results in a gain of 0.9 quality-adjusted life years (QALYs) [4.22 vs. 3.3] at an incremental cost of €9,881. The incremental cost-effectiveness ratio (ICER) of r-maintenance vs. observation is, therefore, estimated at €11,097/QALY gained. The ICER of r-maintenance is sensitive to the duration of treatment benefit and frequency of subsequent treatment; probabilistic sensitivity analysis shows that, over 2000 simulations, the cost/QALY never exceeds €14,000/QALY, a value well below commonly accepted cost-utility thresholds.
Conclusions: In patients with partial or complete response to induction therapy, r-maintenance improves overall survival and progression-free survival and produces more QALYs compared with observation alone, at an acceptable cost/LY and cost/QALY ratio. Maintenance therapy with rituximab is a cost-effective approach for the management of patients with refractory/relapsed follicular lymphoma.
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- 3.Hiddeman W, Unterhalt M. Stand und perspektiven in der therapie follikulare keimzentrumslymphome. Dtsch arzteblatt 1998; 95: heft 50Google Scholar
- 5.Hamblin T, Best H J, Morris J, Hornberger J. Cost-effectiveness of rituximab in treatment of diffuse large B-cell lymphoma. Abstract and poster presented at the 42 British Society of Haematology (BSH) Conference, 20 April 2002, Brighton, United KingdomGoogle Scholar
- 7.Hornberger J, Lewis G. Cost-utility of rituximab in diffuse large B-cell lymphoma. Eur J Cancer 2003; Suppl., vol 1, n∘3 S3 [abstract]Google Scholar
- 8.Malliti M, Junot H, Fievet MH, et al. Treatment of malignant non-Hodgkin’s lymphoma. Economic impact of rituximab (Mabthera) versus conventional chemotherapy. Ann Méd Interne (Paris) 2003; 154: 139–47Google Scholar
- 9.Knight C, Hind D, Brewer N, Abbott V Rituximab (MabThera) for aggressive non-Hodgkin’s lymphoma: systematic review and economic evaluation. Health Technol Assess 2004; 8: iii, ix–xi, 1–82Google Scholar
- 12.Berto P, Morsanutto A, Lopatriello S, et al. Analisi costo-efficacia di rituximab + CHOP versus CHOP in soggetti affetti da linfoma non-Hodgkin aggressivo. Pharmacoeconomics-Italian Research Articles 2004, 6: 151–60Google Scholar
- 17.Wake B, Hyde C, Bryan S, et al. Rituximab as third-line treatment for refractory or recurrent Stage III or IV follicular non-Hodgkin’s lymphoma: a systematic review and economic evaluation. Health Technol Assess 2002; 6: 1–85Google Scholar
- 18.van Oers MH, Klasa R, Marcus RE, et al. Rituximab maintenance improves clinical outcome of relapsed/resistant follicular non-Hodgkin lymphoma in patients both with and without rituximab during induction: results of a prospective randomized phase-3 intergroup trial. Blood 2006; 108: 3295–301PubMedCrossRefGoogle Scholar
- 20.Hainsworth JD, Litchy S, Shaffer DW, et al. Maximizing therapeutic benefit of rituximab: maintenance therapy versus re-treatment at progression in patients with indolent non-Hodgkin’s lymphoma—a randomized phase II trial of the Minnie Pearl Cancer Research Network. J Clin Oncol 2005; 23: 1088–95PubMedCrossRefGoogle Scholar
- 21.Dreyling M, Forstpointner R, Gramatzki M, et al. Rituximab maintenance improves progression-free and overall survival rates after combined immuno-chemotherapy (R-FCM) in patients with relapsed follicular and mantle cell lymphoma: final results of a prospective randomised trial of the German Low Grade Lymphoma Study Group (GLSG). J Clin Oncol 2006; 24 (Suppl.): 7502Google Scholar
- 22.Maturi B, Mikhael J, Dunlop W, et al. Maintenance therapy with rituximab for follicular lymphoma is cost-effective — a Canadian perspective. Proceedings of “ASH-Congress”, Orlando, Florida, 9-12 December, 2006 [abstract]Google Scholar
- 24.Oxford Outcomes Ltd. Utility values in Follicular Lymphoma. 16/12/2005 (data on file).Google Scholar
- 25.Ballatori E, Berto P, Roila F. L’analisi farmacoeconomica in oncologia. Roma: Il Pensiero Scientifico Editore, 1999Google Scholar
- 27.Brazier J, Roberts J, Tsuchiya A. A comparison of the EQ-5D and SF-6D across seven patient groups. Proceedings of the 18th Plenary Meeting of the EuroQol Group Copenhagen. 6th-7th September 2001: 9–33Google Scholar
- 28.Abdalla M, Russell I. Tariffs for the EuroQol health states based on modelling the individual VAS and TTO data of the York survey. EuroQol Plenary Meeting. London, October 1994; 75–93Google Scholar
- 29.www.giorfil.it, accesso luglio 2006
- 30.Ministero della Salute, 1996Google Scholar
- 31.Conferenza delle Regioni e Province Autonome. Tariffa Unica Convenzionale per le prestazioni di assistenza ospedaliera. Regole e tariffe valide per l’anno 2006. Roma, 15 dicembre 2005Google Scholar
- 32.www.ibmdr.galliera.it accesso del 29/08/2006
- 33.www-ministerosalute.it. Schede di Dimissione Ospedaliera, accesso del 29/08/2006
- 35.Dillon A. Managing new health technologies in the UK. In: Atti del Convegno: "Il Technology Assessment: quale influenza sulle scelte istituzionali e quale impatto sul mercato dei farmaci e delle tecnologie e sull’offerta di prestazioni sanitarie". Università L. Bocconi, Milano, 27 ottobre 2005Google Scholar
- 36.Messori A, Santarlasci B, Trippoli S, Vaiani M. Controvalore economico del farmaco e beneficio clinico: stato dell’arte della metodologia di applicazione di un algoritmo farmacoeconomico. Pharmacoeconomics-Italian Research Articles 2003; 5: 53–67Google Scholar
- 37.http://www.eurocambi.com/ riferito a dicembre 2006